Application of Novel Drug Delivery System in Herbal Medicines

• Novel drug delivery system is an advanced drug delivery system targeting the modification of drug release, site specificity, improved drug absorption, reduced side effect profile and increased patient compliance toward the dosage form.
• Hence novel drug delivery systems can provide a new life to the drug molecule.
• Use of Herbal Drugs is increasing worldwide with reference to their effectiveness with lower side effect profiles over their allopathic counterparts.
• India is home to “Ayurveda” have more scope as well as demand for the herbal formulations.
• However the current herbal formulations lack in several areas like,

1. Improper absorption. ( Mostly due to interaction with other substances and partial deactivation by acid/enzymes or by both).
2. Decreased patient compliances. ( Conventional dosage forms are not modified for aesthetic properties like colour, odour, taste etc.).
3. Fluctuations in drug plasma level.
4. Pre-systemic metabolism.
5. Accumulation of drug at non-targeted sites.

• The herbal formulations were considered difficult to incorporate into novel drug delivery systems due to their poly-chemical compositions but after vigorous research, it is made possible.
• In this post, we are going to touch the important delivery systems that can be used for herbal medicines.

1. Liposomes:

• A liposome is a spherical vesicle having at least one lipid bilayer.
• They can have one, several or multiple concentric membranes. Liposomes are constructed of polar lipids which are characterized by having a lipophilic and hydrophilic group of the same molecules.
• Simple examples are detergents, components form micelles, while polar lipids with bulkier hydrophobic parts cannot associate into micelles with high curvature radii but form bilayers which can self-close into liposomes or lipid vesicles.
• A cross-section of a liposome depicts the hydrophilic heads of the amphiphile orienting towards the water compartment while the lipophilic tails orient away from the water towards the centre of the vesicle, thus forming a bilayer.
• Consequently, water-soluble compounds are entrapped in the water compartment and lipid-soluble compounds aggregate in the lipid section.
• Uniquely, liposomes can encapsulate both hydrophilic and lipophilic materials.
• Liposomes usually formed from phospholipids have been used to change the pharmacokinetics profile of, not only drugs but herbs, vitamins and enzymes. 
• Because of their unique properties, liposomes are able to enhance the performance of products by increasing ingredient solubility, improving ingredient bioavailability, enhanced intracellular uptake and altered pharmacokinetics and biodistribution and in vitro and in vivo stability.
• Liposomes as a drug delivery system can improve the therapeutic activity and safety of drugs, mainly by delivering them to their site of action and by maintaining therapeutic drug levels for prolonged periods of time.
• Quercetin an anticancer when entrapped in liposome formulation shown reduced dose and increased blood-brain barrier penetration.

2.  Nanoparticles:

• Nanoparticles and nanoemulsions are colloidal systems with particles varying in size from 10 nm to 1000 nm
• Nanoparticles can be defined as submicronic (b1 lm) colloidal systems.
• The nanospheres have a matrix type structure in which the active ingredient is dispersed throughout (the particles), whereas the nanocapsules have a polymeric membrane and an active ingredient core.
• Nanonization possesses many advantages, such as increasing compound solubility, reducing medicinal doses, and improving the absorbency of herbal medicines compared with the respective crude drugs preparations.
• e.g. nanonized curcuminoids, paclitaxel and praziquantel which have a mean particle size of 450, 147.7, and even higher than 200 nm.

3. Phytosomes:

• Many of the biologically active components of plant origin are polar or say water soluble and hence show lesser absorption.
• A novel approach was introduced by a leading manufacturer by incorporating polar herbal substances into phospholipid sacs and making them more absorbable.
• These lipid macromolecular complexes containing phytoneutrients are called as “Phytosomes”.
• The major difference between the liposomes and phytosomes is chemical bonding.
• In case of the liposomes, the phosphatidyl molecule only surrounds the water-soluble substances.
• In case of the Phytosomes, the phosphatidyl molecule actually forms the chemical bond with the phytoconstituents.
• Phytosomes represent and emerging novel trend in herbal drug delivery systems.

4. Emulsions:

• Emulsions are heterogeneous systems composed of two immiscible liquids and an emulsifying agent mostly a surfactant.
• Emulsions are unstable systems made stable by adding an emulsifying agent.
• In case of emulsions, one liquid is uniformly distributed in the body of another liquid in the form of droplets.
• Depending on droplet size they are categorized as,

1. Micro Emulsions. (10– 100 nm).
2. Sub-micro Emulsions. (100–600 nm).
3. Ordinary Emulsions. (0.1–100 μm)

• The microemulsions are also called as “Nanoemulsions”, while sub microemulsions are also called as “Lipid emulsions”.
• The emulsions as a dosage form can provide targeted drug release, as water-soluble drugs are made as a water in oil type or water in oil in water type (W/O, W/O/W) emulsions while oil-soluble drugs are made as an  Oil in water or oil in water in oil type (O/W, O/W/O).
• The oil-soluble drugs after administration get phagocytized and hence achieve a higher concentration in liver, kidney and spleen.
• Water-soluble drugs after administration get highly concentrated in the lymphatic system however, those given by intramuscular route shows the sustained duration of action where the size of the droplets plays an important role.
• e.g. Emulsion of camphotericin, elememeum emulsion.

5.  Microspheres:

• Administration of medication via microparticulate systems is advantageous because microspheres can be ingested or injected and; they can be tailored for desired release profiles and used site-specific delivery of drugs and in some cases can even provide organ-targeted release.
• So far, a series of plant active ingredients, such as rutin, camptothecin, zedoary oil, tetrandrine, quercetine and Cynara scolymus extract has been made into microspheres.
• In addition, reports on immune microsphere and magnetic microsphere are also common in recent years. Immune microsphere possesses the immune competence as a result of the antibody and antigen was coated or adsorbed on the polymer microspheres.

Microspheres encapsulated herbal formulations.
Formulations	Active ingredients	Applications of formulations	Biological activity	Method of preparation	Size in µm	Route of administration	Reference
Rutin–alginate-chitosan microcapsules	Rutin	Targeting into cardiovascular and cerebrovascular region	Cardiovascular and Cerebrovascular diseases	Complexcoacervation method	165.00– 195.00	In vitro
Zedoary oil microsphere	Zedoary oil	Sustained release and Higher bioavailability	Hepatoprotective	Quasi-emulsion– solvent diffusion method	100– 600	Oral
CPT loaded microspheres	Camptothecin	Prolonged-release of camptothecin	Anticancer	Oil-in-water evaporation method	10	Intraperitoneally and intravenously
Quercetin microspheres	Quercetin	Significantly decreases the dose size	Anticancer	Solvent evaporation	6	In vitro
Cynara scolymus microspheres	Cynara scolymus extract	Controlled release of neutraceuticals	Nutritional supplement	Spray-drying technique	6–7	Oral

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• We have so far seen the present scenario of advancements in novel herbal drug delivery systems however, the area has an extensive scope of research.